Blood pump

ABSTRACT

Apparatus and methods are described including a catheter ( 20 ), a first pump ( 24 U) disposed on the catheter, and a second pump ( 24 D) disposed on the catheter, proximally to the first pump. A control unit ( 52 ) is configured to control activation of the first and second pumps. The first and second pumps are configured, when activated, to pump fluid in opposite directions from one another. Other applications are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a US national phase application of PCTApplication No. PCT/IL/2015/050532 to Schwammenthal (published as WO15/177793), filed May 19, 2015, which:

(a) claims priority from U.S. Provisional Patent Application 62/000,192to Schwammenthal, filed May 19, 2014, entitled “Blood pump;” and

(b) is a continuation-in-part of International Patent ApplicationPCT/IL2014/050289 to Schwammenthal (published as WO 14/141284), filedMar. 13, 2014, entitled “Renal pump,” which claims priority from (a)U.S. Provisional Patent Application 61/779,803 to Schwammenthal, filedMar. 13, 2013, entitled “Renal pump,” and (b) U.S. Provisional PatentApplication 61/914,475 to Schwammenthal, filed Dec. 11, 2013, entitled“Renal pump.”

All of the above-referenced applications are incorporated herein byreference.

FIELD OF EMBODIMENTS OF THE INVENTION

Some applications of the present invention generally relate to medicalapparatus. Specifically, some applications of the present inventionrelate to apparatus and methods associated with placing a pump in one ormore of a subject's renal veins, and/or in the subject's vena cava.

BACKGROUND

It is common for cardiac dysfunction or congestive heart failure todevelop into kidney dysfunction, which in turn, causes congestive heartfailure symptoms to develop or worsen. Typically, systolic and/ordiastolic cardiac dysfunction causes systemic venous congestion, whichgives rise to an increase in renal venous and interstitial pressure. Theincrease in the pressure causes fluid retention by the body to increasedue both to kidney dysfunction and renal neurohormonal activation, bothof which typically develop as a result of the increase in renal venousand interstitial pressure. The resulting fluid retention causescongestive heart failure to develop or worsen, by causing a blood volumeoverload at the heart and/or by increasing systemic resistance.Similarly, it is common for kidney dysfunction and/or renalneurohormonal activation to develop into cardiac dysfunction and/orcongestive heart failure. This pathophysiological cycle, in whichcardiac dysfunction and/or congestive heart failure leads to kidneydysfunction and/or renal neurohormonal activation, or in which kidneydysfunction and/or renal neurohormonal activation leads to cardiacdysfunction and/or congestive heart failure, each dysfunction leading todeterioration in the other dysfunction, is called the cardio-renalsyndrome.

Increased renal venous pressure has been experimentally shown to causeazotemia, and a reduction in glomerular filtration rate, renal bloodflow, urine output, and sodium excretion. It has also been shown toincrease plasma renin and aldosterone, and protein excretion. Venouscongestion may also contribute to anemia via three different pathways: Areduction in the kidney's erythropoietin production, hemodilution byfluid retention, and an inflammatory response leading to a reducedgastro-intestinal iron uptake.

Mechanistically, increased renal venous pressure may cause intracapsularpressure and, subsequently interstitial peritubular pressure, to rise. Arise in peritubular pressure may impact tubular function (reduce sodiumexcretion), as well as diminish glomerular filtration by raising thepressure in the Bowman capsule.

In heart failure patients, increased renal venous pressure may not onlyresult from increased central venous (right atrial) pressure, but alsofrom intraperitoneal fluid accumulations (ascites) exerting directpressure on the renal veins. Reduction of intraabdominal pressure inheart failure patients by removal of fluid (e.g., via paracentesis,and/or ultrafiltration) has been shown to reduce plasma creatininelevels.

Increased venous return resulting from activation of the “leg musclepump” during physical activity such as walking may raise systemic venouspressure, particularly in heart failure patients, and may result inreflux into the renal veins.

SUMMARY OF EMBODIMENTS

In accordance with some applications of the present invention, a subjectis identified as suffering from cardiac dysfunction, congestive heartfailure, reduced renal blood flow, increased renal vascular resistance,arterial hypertension, diabetes, and/or kidney dysfunction. In responsethereto, blood pressure within the subject's renal veins is reduced byplacing at least one pump in the subject's vena cava, and generating alow-pressure region within the subject's vena cava adjacent to junctionsof the vena cava with the subject's renal veins, by activating the pumpto pump blood away from the region. The pump is activated such thatblood pressure within the low-pressure region is lower than centralvenous pressure of the subject. Typically, a downstream pump is placedwithin the vena cava downstream of the junctions of the vena cava withthe subject's renal veins, and the pump pumps blood through the venacava in the downstream direction, away from the junctions. For someapplications, an upstream pump is placed within the vena cava upstreamof the junctions of the vena cava with the subject's renal veins, andthe pump pumps blood through the vena cava in the upstream direction,away from the junctions. Alternatively or additionally, an occlusionelement, such as a balloon or a covered stent is placed in the vena cavaupstream of the junctions, and is configured to partially occlude thevena cava upstream of the junctions.

For some applications, the upstream and downstream pumps are disposed ona single catheter. Typically, the catheter is inserted into the venacava via a venous pathway, e.g., via the femoral vein, via thesubclavian vein, or via the jugular vein. For some applications, theupstream pump, or the occlusion element is disposed on a first catheter,which is inserted via a vein that is below the subject's inferior venacava (e.g., the femoral vein), and the downstream pump is disposed on asecond catheter, which is inserted via a vein that is above thesubject's inferior vena cava (e.g., the subclavian vein, or the jugularvein).

For some applications, the downstream pump and/or the upstream pumpincludes an impeller and a cage. For some applications, impellers of thedownstream and the upstream pumps rotate in the same direction, but thedownstream pump is configured to pump blood in the downstream directionand the upstream pump is configured to pump blood in the upstreamdirection. For some such applications, a single motor is used to impartrotational motion to both of the impellers, and there is a shaftdisposed between the impellers that imparts rotational motion from afirst one of the impellers to a second one of the impellers. Typically,for such applications, the impellers of the upstream and the downstreampumps are (a) of opposing handedness with respect to one another (i.e.,one of the impellers is a left-handed impeller, and the other impelleris a right-handed impeller), and (b) are disposed upon theaforementioned shaft, such that the impellers are facing oppositedirections to one another.

In general, in the specification and in the claims of the presentapplication, the term “proximal” and related terms, when used withreference to a device or a portion thereof, should be interpreted tomean an end of the device or the portion thereof that, when insertedinto a subject's body, is typically closer to a location through whichthe device is inserted into the subject's body. The term “distal” andrelated terms, when used with reference to a device or a portionthereof, should be interpreted to mean an end of the device or theportion thereof that, when inserted into a subject's body, is typicallyfurther from the location through which the device is inserted into thesubject's body.

In general, in the specification and in the claims of the presentapplication, the term “downstream” and related terms, when used withreference to a blood vessel, or with reference to a portion of a devicethat is configured to be placed inside a blood vessel, should beinterpreted to mean a location within the blood vessel, or a portion ofthe device that is intended for placement at a location within the bloodvessel, that is downstream, with respect to the direction of antegradeblood flow through the blood vessel, relative to a different locationwithin the blood vessel. The term “upstream” and related terms, whenused with reference to a blood vessel, or with reference to a portion ofa device that is configured to be placed inside a blood vessel, shouldbe interpreted to mean a location within the blood vessel, or a portionof the device that is intended for placement at a location within theblood vessel, that is upstream with respect to the direction ofantegrade blood flow through the blood vessel, relative to a differentlocation within the blood vessel.

There is therefore provided, in accordance with some applications of thepresent invention, apparatus including:

a catheter;

a first pump disposed on the catheter;

a second pump disposed on the catheter, proximally to the first pump;and

a control unit configured to control activation of the first and secondpumps,

the first and second pumps being configured, when activated, to pumpfluid in opposite directions from one another.

For some applications, the catheter is configured to be placed within avena cava of a subject such that the first pump is disposed downstreamof junctions of the vena cava with all renal veins of the subject, andsuch that the second pump is disposed upstream of junctions of the venacava with all renal veins of the subject.

For some applications, the first and second pumps are configured tolower pressure within the subject's renal veins by:

the first pump pumping blood through the vena cava in a downstreamdirection, and

the second pump pumping blood through the vena cava in an upstreamdirection.

For some applications, the catheter is configured to be placed withinthe subject's vena cava by being inserted via a vein of the subjectselected from the group consisting of: a subclavian vein, a jugularvein, and a femoral vein.

For some applications:

the first pump includes a first impeller configured to pump bloodthrough the vena cava by rotating; and

the second pump includes a second impeller configured to pump bloodthrough the vena cava by rotating.

For some applications,

the apparatus further includes a first cage, the first impeller beingdisposed inside the first cage, and the first cage configured tomaintain a separation between the first impeller and an inner wall ofthe vena cava; and

the apparatus further includes a second cage, the second impeller beingdisposed inside the second cage, and the second cage being configured tomaintain a separation between the second impeller and the inner wall ofthe vena cava.

For some applications, the first and second impellers are configured,when activated, to pump blood in opposite directions from one another bythe first and second impellers being rotated in the same direction asone another, as viewed from an external reference point.

For some applications, the first and second impellers are ofopposing-handedness with respect to one another, and are disposed uponthe catheter such that the impellers face opposite directions from oneanother.

For some applications, the catheter is configured to be placed within ablood vessel of a subject, and the first and second pumps are configuredto generate a region within the blood vessel that is of lower bloodpressure than elsewhere within the blood vessel by pumping blood awayfrom a region of the blood vessel between the first and second pumps.

For some applications, the catheter is configured to be placed within amain vein of a subject into which blood flows from a tributary venoussystem such that:

the first pump is placed in the main vein, downstream of the tributaryvenous system; and

the second pump is placed in the main vein, upstream of the tributaryvenous system.

For some applications, the catheter is configured to be placed within ablood vessel of a subject, and the first and second pumps are configuredto generate a region within the blood vessel that is of higher bloodpressure than elsewhere within the blood vessel by pumping blood towarda region of the blood vessel between the first and second pumps.

For some applications, the catheter is configured to be placed within amain artery of a subject that supplies a branching arterial system thatbranches from the main artery such that:

the first pump is placed in the main artery, downstream of the branchingarterial system; and

the second pump is placed in the main artery, upstream of the branchingarterial system.

For some applications:

the first pump includes a first impeller configured to pump fluid byrotating; and

the second pump includes a second impeller configured to pump fluid byrotating.

For some applications, the first and second impellers are configured,when activated, to pump fluid in opposite directions from one another bythe first and second impellers being rotated in the same direction asone another, as viewed from an external reference point.

For some applications, the first and second impellers are ofopposing-handedness with respect to one another, and are disposed uponthe catheter such that the impellers face opposite directions from oneanother.

For some applications, the apparatus further includes a motor configuredto cause the first and second impellers to pump fluid in oppositedirections from one another by rotating the first and second impellersin the same direction as one another.

There is further provided, in accordance with some applications of thepresent invention, apparatus including:

a catheter;

a first impeller disposed on the catheter; and

a second impeller disposed on the catheter, proximally to the firstimpeller,

longitudinal centers of the first and second impellers being separatedfrom one another by a distance of at least 3 cm, the distance beingmeasured along a longitudinal axis of the catheter.

For some applications, the first and second impellers are ofopposing-handedness with respect to one another, and are disposed uponthe catheter such that the impellers face opposite directions from oneanother.

For some applications, the catheter is configured to be placed within avena cava of a subject such that the first impeller is disposeddownstream of junctions of the vena cava with all renal veins of thesubject, and such that the second impeller is disposed upstream ofjunctions of the vena cava with all renal veins of the subject.

For some applications, the catheter is configured to be placed withinthe subject's vena cava by being inserted via a vein of the subjectselected from the group consisting of: a subclavian vein, a jugularvein, and a femoral vein.

For some applications:

the apparatus further includes a first cage, the first impeller beingdisposed inside the first cage, and the first cage being configured tomaintain a separation between the first impeller and an inner wall ofthe vena cava; and

the apparatus further includes a second cage, the second impeller beingdisposed inside the second cage, and the second cage being configured tomaintain a separation between the second impeller and the inner wall ofthe vena cava.

For some applications,

the apparatus further includes a control unit configured to controlrotation of the first and second impellers, and

the first and second impellers are configured, by rotating, to lowerpressure within the subject's renal veins by:

-   -   the first impeller pumping blood through the vena cava in a        downstream direction, and    -   the second impeller pumping blood through the vena cava in an        upstream direction.

For some applications, the first and second impellers are configured topump fluid in opposite directions from one another by the first andsecond impellers rotating in the same direction as one another, asviewed from an external reference point.

For some applications, the first and second impellers are ofopposing-handedness with respect to one another, and are disposed uponthe catheter such that the impellers face opposite directions from oneanother.

For some applications,

the apparatus further includes a control unit configured to controlrotation of the first and second impellers, and

the first and second impellers are configured to pump fluid in oppositedirections from one another, by the first and second impellers rotatingin the same direction as one another, as viewed from an externalreference point.

For some applications, the first and second impellers are ofopposing-handedness with respect to one another, and are disposed uponthe catheter such that the impellers face opposite directions from oneanother.

For some applications, the apparatus further includes a motor configuredto cause the first and second impellers to pump fluid in oppositedirections from one another by rotating the first and second impellersin the same direction as one another.

For some applications, the catheter is configured to be placed within ablood vessel of a subject, and the first and second impellers areconfigured to generate a region within the blood vessel that is of lowerblood pressure than elsewhere within the blood vessel by pumping bloodaway from a region of the blood vessel between the first and secondimpellers.

For some applications, the catheter is configured to be placed within amain vein of a subject into which blood flows from a tributary venoussystem such that:

the first impeller is placed in the main vein, downstream of thetributary venous system; and

the second impeller is placed in the main vein, upstream of thetributary venous system.

For some applications, the catheter is configured to be placed within ablood vessel of a subject, and the first and second impellers areconfigured to generate a region within the blood vessel that is ofhigher blood pressure than elsewhere within the blood vessel by pumpingblood toward a region of the blood vessel between the first and secondimpellers.

For some applications, the catheter is configured to be placed within amain artery of a subject that supplies a branching arterial system thatbranches from the main artery such that:

the first impeller is placed in the main artery, downstream of thebranching arterial system; and

the second impeller is placed in the main artery, upstream of thebranching arterial system.

There is additionally provided, in accordance with some applications ofthe present invention, apparatus including:

a catheter configured to be placed inside a blood vessel of a subject;

a blood pump disposed on the catheter; and

an occlusion element disposed on the catheter, and configured topartially occlude the subject's blood vessel,

longitudinal centers of the blood pump and the occlusion element beingseparated from one another by a distance of at least 3 cm, the distancebeing measured along a longitudinal axis of the catheter.

For some applications, the blood pump includes an impeller configured topump blood through the subject's blood vessel by rotating.

For some applications, the apparatus further includes a cage, theimpeller being disposed inside the cage, and the cage being configuredto maintain a separation between the impeller and an inner wall of theblood vessel.

For some applications, the catheter is configured to be placed within avena cava of a subject such that the blood pump is disposed downstreamof junctions of the vena cava with all renal veins of the subject, andsuch that the occlusion element is disposed upstream of junctions of thevena cava with all renal veins of the subject.

For some applications, the blood pump is configured to lower pressurewithin the subject's renal veins by pumping blood through the vena cavain a downstream direction.

For some applications, the catheter is configured to be placed withinthe subject's vena cava by being inserted via a vein of the subjectselected from the group consisting of: a subclavian vein, a jugularvein, and a femoral vein.

For some applications, the blood pump includes an impeller configured topump blood through the vena cava by rotating.

For some applications, the apparatus further includes a cage, theimpeller being disposed inside the cage, and the cage being configuredto maintain a separation between the impeller and an inner wall of thevena cava.

For some applications, the blood pump and the occlusion element areconfigured to generate a region within the blood vessel that is of lowerblood pressure than elsewhere within the blood vessel by the blood pumppumping away from a region of the blood vessel between the blood pumpand the occlusion element.

For some applications, the catheter is configured to be placed within amain vein of a subject into which blood flows from a tributary venoussystem such that:

the blood pump is placed in the main vein, downstream of the tributaryvenous system; and

the occlusion element is placed in the main vein, upstream of thetributary venous system.

For some applications, the blood pump and occlusion element areconfigured to generate a region within the blood vessel that is ofhigher blood pressure than elsewhere within the blood vessel by theblood pump pumping blood toward a region of the blood vessel between theblood pump and the occlusion element.

For some applications, the catheter is configured to be placed within amain artery of a subject that supplies a branching arterial system thatbranches from the main artery such that:

the occlusion element is placed in the main artery, downstream of thebranching arterial system; and

the blood pump is placed in the main artery, upstream of the branchingarterial system.

There is further provided, in accordance with some applications of thepresent invention, a method for use with a tributary venous system of asubject that flows into a main vein of the subject, the methodincluding:

reducing blood pressure within the tributary venous system by:

-   -   placing a first pump in the main vein, downstream of the        tributary venous system, and activating the first pump to pump        blood through the main vein in a downstream direction; and    -   placing a second pump in the main vein, upstream of the        tributary venous system, and activating the second pump to pump        blood through the main vein in an upstream direction.

For some applications, the first and second pumps are disposed upon asingle catheter, and placing the first and second pumps in the main veinincludes inserting a distal end of the catheter into the main vein.

For some applications:

the main vein includes a vena cava of the subject,

the tributary venous system includes a renal venous system of thesubject,

placing the first pump in the main vein, downstream of the tributaryvenous system, includes placing the first pump in the vena cava,downstream of junctions of the vena cava with all renal veins of thesubject,

placing the second pump in the main vein, upstream of the tributaryvenous system, includes placing the second pump in the vena cava,upstream of the junctions of the vena cava with all of the subject'srenal veins,

the method further includes identifying the subject as suffering from acondition selected from the group consisting of: cardiac dysfunction,congestive heart failure, reduced renal blood flow, increased renalvascular resistance, arterial hypertension, and kidney dysfunction, and

reducing pressure within the tributary venous system includes reducingpressure within renal veins of the subject, in response to theidentifying.

For some applications, the first and second pumps are disposed upon asingle catheter, and placing the first and second pumps in the vena cavaincludes inserting a distal end of the catheter into the subject's venacava.

For some applications, inserting the distal end of the catheter into thesubject's vena cava includes inserting the distal end of the catheterinto the subject's vena cava via a vein of the subject selected from thegroup consisting of: a subclavian vein, a jugular vein, and a femoralvein.

For some applications:

placing the first pump in the main vein includes placing a firstimpeller in the main vein, downstream of the tributary venous system;and

placing the second pump in the main vein includes placing a secondimpeller in the main vein, upstream of the tributary venous system.

For some applications:

placing the first impeller inside the main vein includes inserting thefirst impeller into the main vein while the first impeller is disposedinside a cage that is configured to maintain a separation between thefirst impeller and an inner wall of the main vein; and

placing the second impeller inside the main vein includes inserting thesecond impeller into the main vein while the second impeller is disposedinside a cage that is configured to maintain a separation between thesecond impeller and the inner wall of the main vein.

For some applications, activating the first pump to pump blood throughthe main vein in the downstream direction includes rotating the firstimpeller in a given direction, and activating the second pump to pumpblood through the main vein in the upstream direction includes rotatingthe second impeller in the same given direction, as viewed from anexternal reference point.

For some applications, the first and second impellers are ofopposing-handedness to one another, and are disposed upon a singlecatheter such that the first and second impellers face in oppositedirections from another, and placing the first and second pumps in thevena cava includes inserting a distal end of the catheter into thesubject's vena cava.

For some applications, rotating the first and second impellers in thegiven direction includes using a single motor to rotate the first andsecond impellers.

There is additionally provided, in accordance with some applications ofthe present invention, a method for use with a tributary venous systemof a subject that flows into a main vein of the subject, the methodincluding:

reducing blood pressure within the tributary venous system by:

-   -   placing a pump in the main vein, downstream of the tributary        venous system, and activating the pump to pump blood through the        main vein in a downstream direction; and    -   placing an occlusion element in the main vein at a location        within the main vein that is upstream of the tributary venous        system, such that the occlusion element partially occludes the        main vein at the location.

For some applications, placing the occlusion element in the main veinincludes placing a balloon in the main vein.

For some applications, placing the occlusion element in the main veinincludes placing a frame that is covered with a blood-impermeablematerial in the main vein.

For some applications, the pump and the occlusion element are disposedupon a single catheter, and placing the pump and the occlusion elementin the main vein includes inserting a distal end of the catheter intothe main vein.

For some applications:

the main vein includes a vena cava of the subject,

the tributary venous system includes a renal venous system of thesubject,

placing the pump in the main vein, downstream of the tributary venoussystem includes placing the pump in the vena cava, downstream ofjunctions of the vena cava with all renal veins of the subject,

placing the occlusion element in the main vein at the location withinthe main vein that is upstream of the tributary venous system includesplacing the occlusion element in the vena cava upstream of the junctionsof the vena cava with all of the subject's renal veins,

the method further includes identifying the subject as suffering from acondition selected from the group consisting of: cardiac dysfunction,congestive heart failure, reduced renal blood flow, increased renalvascular resistance, arterial hypertension, and kidney dysfunction, and

reducing pressure within the tributary venous system includes reducingpressure within renal veins of the subject, in response to theidentifying.

For some applications, the pump and the occlusion element are disposedupon a single catheter, and placing the pump and the occlusion elementin the vena cava includes inserting a distal end of the catheter intothe vena cava.

For some applications, inserting the distal end of the catheter into thevena cava includes inserting the distal end of the catheter into thevena cava via a vein of the subject selected from the group consistingof: a subclavian vein, a jugular vein, and a femoral vein.

For some applications, placing the pump in the main vein includesplacing an impeller in the main vein, downstream of the tributary venoussystem.

For some applications, placing the impeller inside the main veinincludes inserting the first impeller into the main vein while theimpeller is disposed inside a cage that is configured to maintain aseparation between the first impeller and an inner wall of the mainvein.

There is further provided, in accordance with some applications of thepresent invention, a method including:

identifying a subject as suffering from a condition selected from thegroup consisting of: cardiac dysfunction, congestive heart failure,reduced renal blood flow, increased renal vascular resistance, arterialhypertension, and kidney dysfunction; and

in response thereto, reducing blood pressure within renal veins of thesubject, by:

-   -   placing at least one pump in a vena cava of the subject; and    -   generating a low-pressure region within the subject's vena cava,        adjacent to junctions of the vena cava with the subject's renal        veins, blood pressure within the low-pressure region being lower        than central venous pressure of the subject,    -   by activating the at least one pump to pump blood away from the        region.

For some applications, generating the low-pressure region within thesubject's vena cava includes:

placing a blood-impermeable sleeve in the subject's vena cava, such thata downstream end of the sleeve is coupled to a wall of the vena cava ata first location that is downstream of all of the renal veins of thesubject, and such that an upstream end of the sleeve is coupled to thewall of the vena cava at a second location that is upstream of all therenal veins of the subject; and

activating the pump to pump blood from a location outside the sleevethat is in fluid communication with the subject's renal veins, to alocation within the vena cava that is in fluid communication with aninterior of the sleeve.

For some applications:

placing the at least one pump in the subject's vena cava includes:

-   -   placing a first pump in the vena cava, downstream of junctions        of the vena cava with all renal veins of the subject; and    -   placing a second pump in the vena cava, upstream of the        junctions of the vena cava with all of the subject's renal        veins; and        generating the low-pressure region within the subject's vena        cava includes:    -   activating the first pump to pump blood through the vena cava in        a downstream direction; and    -   activating the second pump to pump blood through the vena cava        in an upstream direction.

For some applications:

placing the at least one pump in the subject's vena cava includes:

-   -   placing a pump in the vena cava, downstream of junctions of the        vena cava with all renal veins of the subject; and    -   placing an occlusion element in the vena cava at a location        within the vena cava that is upstream of the junctions of the        vena cava with all of the subject's renal veins, such that the        occlusion element partially occludes the vena cava at the        location; and

generating the low-pressure region within the subject's vena cavaincludes activating the pump to pump blood through the vena cava in adownstream direction.

For some applications, placing the occlusion element in the vena cavaincludes placing a balloon in the vena cava.

For some applications, placing the occlusion element in the vena cavaincludes placing in the vena cava a frame that is covered with ablood-impermeable material.

The present invention will be more fully understood from the followingdetailed description of embodiments thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-D are schematic illustrations of a blood-pump catheter placedwithin a subject's vena cava, an upstream pump being disposed upon thecatheter, distally to a downstream pump, in accordance with someapplications of the present invention;

FIG. 2 is a schematic illustration of the catheter of FIGS. 1A-Dinserted into the subject's vena cava via the subject's right jugularvein, in accordance with some applications of the present invention;

FIG. 3 is a schematic illustration of a blood-pump catheter insertedinto a subject's vena cava via the subject's femoral vein, a downstreampump being disposed upon the catheter distally to an upstream pump, inaccordance with some applications of the present invention;

FIG. 4 is a schematic illustration of upstream and downstream pumpsdisposed on respective blood-pump catheters, in accordance with someapplications of the present invention;

FIGS. 5A-B are schematic illustrations of a catheter that includes adownstream pump and an occlusion element, such as a balloon (FIG. 5A),or a covered frame (FIG. 5B), in accordance with some applications ofthe present invention; and

FIG. 6 is a schematic illustration of a blood-impermeable sleeveconfigured to occlude blood flow from a subject's vena cava to thesubject's renal veins, as described in WO 14/141284, which isincorporated herein by reference, and in accordance with someapplications of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-D, which are schematic illustrations of ablood-pump catheter 20 placed within a subject's vena cava 22, via aguide catheter 23, an upstream pump 24U being disposed upon thecatheter, distally to a downstream pump 24D, in accordance with someapplications of the present invention. Typically, the distal portion ofblood-pump catheter 20 is configured to be straight, when the catheteris in a non-constrained state, such that both the upstream and thedownstream pumps are disposed along the axis of the catheter, within thevena cava.

Each of the upstream and downstream pumps 24U and 24D typically includesa radially-expandable impeller 28 disposed inside a radially-expandableimpeller cage 30. Typically, impeller 28 and cage 30 are shape set suchas to assume radially-expanded configurations thereof in the absence ofany radially-constraining force acting upon the impeller and the cage.Further typically, an engagement mechanism engages the impeller and thecage with respect to one another, such that in response to the cagebecoming radially constrained the impeller becomes radially constrained,e.g., in accordance with apparatus and methods described in described inWO 14/141284 to Schwammenthal, which is incorporated herein byreference.

It is noted that the term “impeller” is used herein to denote a bladedrotor, as shown in 1A-D, for example. When the bladed rotor is placedinside a blood vessel (such as vena cava 22) and rotated, the bladedrotor functions as an impeller, by modifying the flow of blood throughthe blood vessel, and/or by generating a pressure difference between theupstream end and the downstream end of the impeller.

It is noted that reference numeral 24 is generally used to denote ablood pump in the present application. When a pump that is placedupstream is being referred to, reference numeral 24U is used, and when apump that is placed downstream is being referred to, reference numeral24D is used. Similarly, reference numeral 28 is generally used to denotean impeller in the present application. When an impeller that is placedupstream is being referred to, reference numeral 28U is used, and whenan impeller that is placed downstream is being referred to, referencenumeral 28D is used.

Blood-pump catheter 20 is typically placed inside the subject's venacava 22, and operated therein, in order to provide acute treatment of asubject suffering from cardiac dysfunction, congestive heart failure,low renal blood flow, high renal vascular resistance, arterialhypertension, diabetes, and/or kidney dysfunction. For example, theblood-pump catheter may be placed inside the subject's vena cava, andoperated therein, for a period of more than one hour (e.g., more thanone day), less than one week (e.g., less than four days), and/or betweenone hour and one week (e.g., between one day and four days). For someapplications, the blood-pump catheter is chronically placed inside thesubject's vena cava in order to provide chronic treatment of a subjectsuffering from cardiac dysfunction, congestive heart failure, low renalblood flow, high renal vascular resistance, arterial hypertension,diabetes, and/or kidney dysfunction. For some applications, a course oftreatment is applied to a subject over several weeks, several months, orseveral years, during which the blood-pump catheter is intermittentlyplaced inside the subject's vena cava, and the subject is intermittentlytreated in accordance with the techniques described herein. For example,the subject may be intermittently treated at intervals of several days,several weeks, or several months.

For some applications, blood-pump catheter 20 is inserted into vena cava22, via the subject's subclavian vein 40, as shown in FIG. 1A.Typically, the blood-pump catheter is inserted under fluoroscopicimaging. Alternatively, the blood-pump catheter is inserted underultrasound imaging, such as to reduce exposure of the subject toradiation and/or contrast agent. The catheter is placed into the venacava such that upstream pump 24U is disposed upstream of the junctionsof the vena cava and all of the subject's renal veins 42, and such thatdownstream pump 24D is disposed downstream of the junctions of the venacava and all of the subject's renal veins. Typically, the upstream pumpis configured to pump blood through the vena cava in the upstreamdirection, away from the renal veins, and the downstream pump isconfigured to pump blood through the vena cava in the downstreamdirection, away from the renal veins.

The effect of both of pumps 24U and 24D pumping blood in theabove-described manner is that, between the pumps, and adjacent to thejunctions of the vena cava with the renal veins, there is a low-pressureregion of the vena cava, within which blood pressure is lower than thesubject's central venous pressure. Functionally, this region may beviewed as a compartment within the vena cava within which blood pressureis controlled (by controlling pumps 24U and 24D), regardless of theblood pressure elsewhere within the vena cava. This typically increasesblood flow from the renal veins into the vena cava, lowers pressurewithin the subject's renal veins, and causes renal perfusion toincrease. The effect of pumps 24U and 24D on blood flow through therenal veins and the vena cava is indicated by arrows 44 in FIG. 1B.

As described hereinabove, the effect of operating blood pumps 24U and24D is that between the pumps there is a low-pressure region of the venacava. However, typically, the pumps are operated simultaneously suchthat the pressure within other portions of the vena cava issubstantially unchanged relative to when blood-pump catheter 20 is notin operation. For example, the pumps are typically operatedsimultaneously such that the pressure within the vena cava downstream ofdownstream pump 24D is not substantially increased relative to whenblood-pump catheter 20 is not in operation. Similarly, the pumps aretypically operated simultaneously such that the pressure within the venacava upstream of upstream pump 24U is not substantially increasedrelative to when blood-pump catheter 20 is not in operation. This isbecause the pumps are typically operated simultaneously such thatoutside of the region between the two pumps, the effects of the pumpingby the upstream and downstream pumps cancel each other with respect topressure. It is noted that there is likely to be some increase in thepressure within the vena cava downstream of downstream pump and upstreamof upstream pump due to the increased blood flow from the renal veinsinto the vena cava.

Similarly, the pumps are typically operated simultaneously such thatvenous return to the vena cava from regions upstream of the upstreampump and downstream from the downstream pump is substantially unchangedrelative to when blood-pump catheter 20 is not in operation. In thismanner, the pumps the pumps are typically operated simultaneously suchas to have a generally synergistic effect on pressure and flow in theregion between the pumps, but to have an antagonistic effect on pressureand flow outside of the region, such that, outside of the region, theeffects of the two pumps typically substantially cancel each other.

Typically, blood-pump catheter 20 pumps blood in a manner that enhancesthe rate of flow of blood flow through the renal veins and into the venacava, but does not cause a substantial change in the direction of theblood flow relative to the natural direction of flow through the renalveins, or from the renal veins to the vena cava (i.e., relative to bloodflow in the absence of pumping by the blood-pump catheter). That is tosay that the blood-pump catheter pumps blood in the downstream directionthrough the renal veins and then directly into the portion of the venacava that is adjacent to the renal veins, rather than, for example,pumping the blood from the renal veins into a different portion of thesubject's veins (such as, an upstream location within the vena cava). Itis noted that, due to the pumping of the downstream pump in thedownstream direction, there is likely to be some blood flow from therenal veins to the portion of the vena cava that is below the renalveins. Further typically, blood-pump catheter 20 enhances blood flowthrough the renal veins without removing blood from the subject's venoussystem into a non-venous receptacle, such as an artificial lumen of ablood pump.

As described hereinabove, typically blood-pump catheter 20 is placedinside the vena cava of a subject suffering from cardiac dysfunction,congestive heart failure, low renal blood flow, high renal vascularresistance, arterial hypertension, diabetes, and/or kidney dysfunction.Typically, operating the blood-pump catheter in the vena cava of such asubject causes a lowering and flattening of the subject's renal veinpressure profile, even though the subject's central venous pressure iselevated, e.g., as described with reference to FIG. 4B of WO 14/141284to Schwammenthal, which is incorporated herein by reference.

Typically, due to the reduction in pressure in the renal vein that iscaused by the pumping of blood by blood-pump catheter 20, perfusion ofthe kidney increases. In turn, this may cause pressure in the renalveins to rise relative to the pressure in the renal veins immediatelysubsequent to initiation of the pumping, due to increased blood flowinto the renal vein. Typically, even after perfusion of the kidneyincreases, the pump is configured to maintain the pressure in the renalvein at a lower value than the pressure in the renal vein before theinitiation of the pumping. For some applications, in addition tolowering the subject's renal vein pressure, and/or increasing perfusionof the subject's kidney, blood-pump catheter 20 performs ultrafiltrationon the subject's blood.

It is noted that, for some applications, due to the reduction inpressure in the renal vein that is caused by the pumping of blood byblood-pump catheter 20, the subject's renal vascular resistancedecreases, in accordance with physiological mechanisms that aredescribed, for example, in an article by Haddy et al., entitled “Effectof elevation of intraluminal pressure on renal vascular resistance”(Circulation Research, 1956), which is incorporated herein by reference.It is further noted that a treatment of the subject that increases renalperfusion by increasing blood pressure in the subject's renal arterieswould typically not effect the aforementioned physiological mechanisms.

Typically, when blood-pump catheter 20 is used to reduce pressure in thesubject's renal veins, it is expected that there will be an improvedresponsiveness by the subject to administration of diuretics to thesubject, due to the reduction in renal venous pressure. Therefore, forsome applications, a reduced dosage of diuretics may be administered tothe subject relative to a dosage of diuretics that would be administeredto the subject in the absence of performing the techniques describedherein. Alternatively, a regular dosage of diuretics may be administeredto the subject, but the diuretics may have a greater effect on thesubject, due to the reduction in renal venous pressure.

Typically, high central venous pressure leads to a high level of bloodpressure within the heart, which in turn leads to the release of atrialnatriuretic peptide (ANP) and B-type natriuretic peptide (BNP) by thesubject, both of which act as natural diuretics. For some applications,when blood-pump catheter 20 is used to reduce pressure in the subject'srenal veins, there is expected to be an improved responsiveness by thesubject to the release of the natural diuretics by the subject, due tothe reduction in renal venous pressure. For some applications, since thesubject's central venous pressure is not lowered by using blood-pumpcatheter 20, it is expected that the subject will continue to releaseatrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP),even while the subject's renal venous pressure is reduced by the use ofthe blood pumps. Thus, for some applications, using blood-pump catheter20 may result in the subject continuing to release atrial natriureticpeptide (ANP) and B-type natriuretic peptide (BNP), as well as resultingin the effectiveness of the aforementioned natural diuretics beinggreater than the effectiveness of the diuretics in the absence of theuse of blood-pump catheter 20.

Typically, each of upstream and downstream pumps 24U and 24D includes animpeller 28, for example, any one of the impellers described in WO14/141284 to Schwammenthal, which is incorporated herein by reference.In accordance with respective applications, impeller 28 may have asingle blade, two blades (e.g., as described in WO 14/141284 toSchwammenthal, which is incorporated herein by reference), three blades(e.g., as described in WO 14/141284 to Schwammenthal, which isincorporated herein by reference), or more than three blades. For someapplications, one or both of blood pumps 24U and 24D includes more thanone impeller. Typically, ceteris paribus, by using more than oneimpeller in at least one of the pumps, in order to generate a given flowof blood with the pump, the force that impacts each of the impellerswithin the pump is smaller than if a single impeller were to be used inthe pump.

For some applications, one or both of the pumps includesradially-expandable cage 30. Typically, cage 30 is configured to holdopen the inner wall of the vena cava and to separate the inner wall ofthe vena cava from the impeller, such that the vena cava does not becomeinjured by the impeller. As described hereinabove, typically, impeller28 and 30 are shape set such as to assume radially-expandedconfigurations thereof in the absence of any radially-constraining forceacting upon the impeller and/or the cage. Further typically, anengagement mechanism engages the impeller and the cage with respect toone another, such that in response to the cage becoming radiallyconstrained the impeller becomes radially constrained, e.g., inaccordance with apparatus and methods described in described in WO14/141284 to Schwammenthal, which is incorporated herein by reference.

Referring now to FIG. 1C, typically, when blood-pump catheter 20 isplaced inside vena cava 22, impeller 28 and cage 30 are substantiallynot radially constrained, due to the relatively low radial force exertedby the vena cava wall on the cage. Typically, a span SP of impeller 28,when the impeller is in a non-constrained configuration thereof insidethe vena cava is more than 14 mm (e.g., more than 16 mm), and/or lessthan 28 mm (e.g., less than 22 mm), e.g., 14-28 mm, or 16-22 mm.Typically, a diameter D of cage 30, when the cage is in anon-constrained configuration thereof inside the vena cava is more than14 mm (e.g., more than 16 mm), and/or less than 40 mm (e.g., less than35 mm), e.g., 14-40 mm, or 16-35 mm. Further typically, when blood-pumpcatheter 20 is used to enhance blood flow from the renal veins into thesubject's vena cava, as described herein, a longitudinal distance D1between centers of the impellers of the upstream and downstream pumps,measured along the longitudinal axis of the catheter, is typically morethan 3 cm (e.g., more than 6 cm), and/or less than 18 cm (e.g., lessthan 14 cm), e.g., 3-18 cm, or 6-14 cm.

Typically, impellers of pumps 24U and 24D are coupled to one or moremotors 46 (FIG. 1A), which impart rotational motion to the impellers,via one or more shafts, the shaft(s) being housed inside blood-pumpcatheter 20. In accordance with respective applications, the motors aredisposed outside of the subject's body (as shown), or are placed insidethe subject's body (not shown).

For some applications, in order for the impellers to pump blood inopposite directions (i.e., in order for the upstream impeller to pumpblood upstream, and the downstream pump to pump blood downstream), theimpellers are rotated in opposite directions from one another, as viewedfrom an external reference point.

Referring now to FIG. 1D, typically, impellers 28 of upstream anddownstream pumps 24U and 24D are rotated in the same rotationaldirection as one another, as viewed from an external reference point(e.g., in the direction of arrow 48 (i.e., clockwise), orcounterclockwise), but the impellers are disposed on the catheter suchthat the rotation of the impellers in this direction of rotation causesthe impellers to pump blood in respective, opposite directions. It isnoted that the rotational direction of the impellers “as viewed from anexternal reference point” should be interpreted to mean the direction ofrotational motion of the impellers as observed from any point that isnot undergoing the same rotational motion as either of the impellers.(For illustrative purposes, FIG. 1D shows the impellers in the absenceof the cages, although typically, the impellers are used together withcages, as described hereinabove.)

Typically, for such applications, a single motor is used to rotate bothof the impellers. A shaft 50 is used to impart the rotational motionfrom the motor to the proximal impeller. An additional shaft 51, whichis in series with shaft 50, couples the proximal impeller to the distalimpeller and imparts the rotational motion from the proximal impeller tothe distal impeller. For some applications, by using a single series ofshafts to impart rotation to impellers 28 of both upstream anddownstream pumps 24U and 24D, the diameter of blood-pump catheter 20 isreduced relative to if parallel shafts were used, in order to impartrotation to the upstream and downstream impellers.

For some applications, the angles and/or orientations of the impellerblades of impellers 28 of upstream and downstream pumps 24U and 24D maybe such as to cause the impellers to pump blood in respective, oppositedirections. For some applications, as shown in FIG. 1D, each propelleris shaped and/or oriented in the mirror image of the other, the axis ofreflection being orthogonal to the longitudinal axes of the impellers.Typically, the upstream and downstream impellers are ofopposing-handedness to one another, a first one of the impellers being aleft-handed impeller, and the other one of the impellers being aright-handed impeller. It is generally the case that impellers ofopposing handedness that are positioned parallel to one another, facingthe same direction as one another, and rotating in opposite rotationaldirections from one another, generate flow in the same direction as oneanother. In accordance with the present invention, the upstream anddownstream impellers are typically disposed upon shaft 51 such that theimpellers are facing in opposite directions to one another. As describedhereinabove, the impellers are typically rotated in the same rotationaldirection as one another, as viewed from an external reference point.The result of the impellers (a) being of opposing handedness to oneanother, and (b) facing in opposite directions, is that, when theimpellers are rotated in the same direction as one another about an axisdefined by shaft 51, the impellers pump blood in opposite directionsfrom one another.

Typically, the blades of the downstream impeller are oriented such that,as the downstream impeller rotates in the direction of arrow 48, thedownstream impeller pumps in the downstream direction. The blades of theupstream impeller are oriented such that, as the upstream impellerrotates in the direction of arrow 48, the upstream impeller pumps in theupstream direction.

As described in further detail hereinbelow, for some applications,upstream and downstream pumps 24U and 24D and blood-pump catheter 20 areplaced within a main artery upstream and downstream of bifurcations ofthe artery with one or more branching arterial systems that branch fromthe main artery and supply a given organ, mutatis mutandis. For suchapplications, the blades of the downstream impeller are oriented suchthat, as the downstream impeller is rotated, the downstream impellerpumps in the upstream direction (toward the bifurcations). The blades ofthe upstream impeller are oriented such that, as the upstream impellerrotates is rotated, the upstream impeller pumps in the downstreamdirection (toward the bifurcations), such that blood flow into thebranching arterial system is increased, thereby increasing perfusion ofthe organ.

For some applications, the blades of the impellers of the upstream anddownstream pumps are configured to pump blood in the same direction asone another (e.g., in the antegrade direction). For example, theimpellers may be of the same handedness as one another, placed uponcatheter 20 such that the impellers are facing in the same direction asone another, and rotated in the same direction as one another, as viewedfrom an external reference point. Alternatively, the two impellers maybe of opposing handedness to one another, placed within the vena cavasuch that the two impellers are facing in the same direction as oneanother, and rotated in opposite directions to one another, as viewedfrom an external reference point.

For some applications, blades of the upstream and downstream impellersare disposed at an angle alpha with respect to the longitudinal axes ofthe impellers, the blades of the respective impellers being oriented inopposite directions. For some applications, angle alpha is greater than15 degrees (e.g., greater than 25 degrees), and/or less than 45 degrees(e.g., less than 35 degrees), e.g. 15-45 degrees, or 25-35 degrees.

For some applications, impellers 28 of upstream and downstream pumps 24Uand 24D are rotated at respective rotation rates, in order to cause thepumping of blood in the upstream and downstream directions to beperformed at respective rates. Alternatively, the impellers are rotatedat the same rotation rate (and, typically, in the same direction), butthe impellers are sized, shaped, and/or oriented such that the rate atwhich blood is pumped, respectively, in the upstream and downstreamdirections, by the respective impellers, is not equal.

Typically, a control unit 52 and a user interface 54 are disposedoutside the subject's body. Further typically, the control unit receivesinputs from one or more pressure sensors 56, 58, and/or 60, e.g., asshown in FIGS. 1A-D.

In accordance with some applications:

(a) a pressure sensor 56 is disposed on the upstream side of upstreamblood pump 24U and is configured to measure pressure within the venacava upstream of the low-pressure region of the vena cava, which istypically indicative of venous pressure within the subject's lower body;

(b) a pressure sensor 58 disposed between the two blood pumps, and isconfigured to measure pressure within the low-pressure region of thevena cava between the two blood pumps, which is typically indicative ofblood pressure within the subject's renal veins; and/or

(c) a pressure sensor 60 is disposed on the downstream side ofdownstream blood pump 24D and is configured to measure pressure withinthe vena cava downstream of the low-pressure region of the vena cava,which is typically indicative of the subject's central venous pressureclose the subject's right heart.

For some applications, blood-pump catheter 20 includes pressure sensor58 disposed between the two blood pumps, and is configured to measurepressure within the low-pressure region of the vena cava between the twoblood pumps, which is typically indicative of blood pressure within thesubject's renal veins, and the blood-pump catheter does not includepressure sensor 56, or pressure sensor 60.

For some applications, control unit 52 controls pumps 24U and 24D, e.g.,by controlling rotation of impellers 28, responsively to one or more ofthe above-described inputs. Typically, user interface 54 displays thesubject's current lower-body venous pressure, renal venous pressure,and/or central venous pressure, based upon the signals generated bysensors 56, 58, and/or 60. Typically, based upon the current values ofthe subject's lower-body venous pressure, renal venous pressure, and/orcentral venous pressure, a user (such as a healthcare professional)inputs a target value for the subject renal venous pressure, via theuser interface. In response thereto, control unit 52 controls the speedof the rotation of the impellers, such that the impellers pump bloodaway from the renal veins at a flow rate that is such as to reduce therenal venous pressure toward the target level, as indicated by the user.For some applications, in response a signal received from sensor 60indicating that the central venous pressure is at the target renalvenous pressure, the control unit stops the impellers rotating. For someapplications, the control unit receives an input from an additionalsensor (such as a flow sensor and/or an oxygen-saturation sensor, and/ora thermal flow sensor, e.g., as described with reference to FIGS.22Ai-22Cii of WO 14/141284 to Schwammenthal, which is incorporatedherein by reference), and the control unit controls the speed of therotation of the impellers responsively to an input from the additionalsensor.

It is noted that control unit 52 typically includes a computer processorthat comprises circuitry and that is configured to execute the actionsdescribed herein. Typically, the operations described herein that areperformed by the computer processor transform the physical state of amemory, which is a real physical article that is in communication withthe computer processor, to have a different magnetic polarity,electrical charge, or the like depending on the technology of the memorythat is used. Control unit 52 is typically a hardware device programmedwith computer program instructions to produce a special purposecomputer. For example, when programmed to perform the techniquesdescribed herein, control unit 52 typically acts as a special purposerenal-venous-pressure-modulating computer processor.

It is further noted that user interface 54 typically includes any typeof user interface configured to receive inputs from a user and/or toprovide outputs to the user. For example, the user interface may includeone or more input devices (such as a keyboard, a mouse, a trackball, ajoystick, a touchscreen monitor, a touchpad, a voice-command interface,a smartphone, a tablet computer, and/or other types of input devicesthat are known in the art), and/or one or more output devices (such as amonitor, an audio output device, a smartphone, a tablet computer, and/orother types of output devices that are known in the art).

Reference is now made to FIG. 2, which is a schematic illustration ofblood-pump catheter 20 being inserted into the subject's vena cava 22via the subject's right jugular vein 62 (through guide catheter 23), inaccordance with some applications of the present invention. For someapplications, instead of being inserted via the subclavian vein (asshown in FIG. 1A, for example), blood-pump catheter 20 is inserted intothe vena cava via the subject's right jugular vein, or via another veinthat is above the subject's inferior vena cava. In all other aspects,blood-pump catheter 20 and the functioning thereof are generally asdescribed with reference to FIGS. 1A-D.

Reference is now made to FIG. 3, which is a schematic illustration ofblood-pump catheter 20 being inserted into the subject's vena cava 22via the subject's femoral vein 64 (through guide catheter 23),downstream pump 24D being disposed upon the catheter distally toupstream pump 24U, in accordance with some applications of the presentinvention. For some applications, instead of being inserted via thesubclavian vein (as shown in FIG. 1A, for example), blood-pump catheter20 is inserted into the vena cava, via the subject's femoral vein 64, orvia another vein that is below the subject's inferior vena cava.Typically, downstream blood pump 24D is disposed on blood-pump catheter20 distally to upstream blood pump 24U. Blood-pump catheter 20 isconfigured to be placed within the vena cava, such that the upstreampump is disposed upstream of the junctions of the vena cava with all ofthe subject's renal veins 42, and such that the downstream pump isdisposed downstream of the junctions of the vena cava with all of thesubject's renal veins. Other than the dispositions of the upstream anddownstream blood pumps with respect to blood-pump catheter 20,blood-pump catheter 20, as shown in FIG. 3, and the functioning thereof,is generally similar to that described with reference to blood-pumpcatheter 20 as shown in FIGS. 1A-D.

Reference is now made to FIG. 4, which is a schematic illustration ofupstream and downstream pumps 24 U and 24D being disposed on respectivecatheters 66 and 68, in accordance with some applications of the presentinvention. For some applications, a first catheter 66 is inserted intovena cava 22 through a guide catheter 67 that is inserted via thesubject's femoral vein 64, or via another vein that is below thesubject's inferior vena cava. Upstream blood pump 24U is disposed on thefirst catheter, and is configured to be placed within the vena cavaupstream of the junctions of the vena cava with all of the subject'srenal veins, and to pump blood through the vena cava in the mannerdescribed hereinabove. A second catheter 68 is inserted into the venacava through a guide catheter 69 that is inserted via the subject'sjugular vein 62 (as shown), via the subclavian vein (not shown), or viaa different vein that is above the subject's inferior vena cava.Downstream blood pump 24D is disposed on the second catheter, and isconfigured to be placed within the vena cava downstream of the junctionsof the vena cava with all of the subject's renal veins, and to pumpblood through the vena cava in the manner described hereinabove.

For applications in which the upstream and downstream blood pumpsinclude impellers, typically, respective motors 70 and 72 are used tocontrol rotation of the impellers. Further typically, control unit 52controls both pumps (e.g., by controlling the rates of rotation of theimpellers). For some applications, pressure sensors 56, 58 and 60 aredisposed upon the first and/or second catheters, and are configured todetect indications of, respectively, lower body venous pressure, renalvenous pressure, and central venous pressure. The control unit isconfigured to control the operation of the upstream and downstream pumpsresponsively to the detected indications, in accordance with thetechniques described hereinabove.

Reference is now made to FIGS. 5A-B, which are schematic illustrationsof blood-pump catheter 20, the catheter including downstream pump 24Dand an occlusion element, such as a balloon 80 (FIG. 5A), or a coveredframe 82 (FIG. 5B), in accordance with some applications of the presentinvention. For some applications, downstream pump is placed inside venacava 22, downstream of the junctions of the vena cava with all of thesubject's renal veins. The downstream pump pumps blood through the venacava, in the downstream direction, away from the junctions of the venacava with the renal veins, in the manner described hereinabove. As analternative to, or in addition to using an upstream pump as describedhereinabove, the occlusion element is placed inside the vena cavaupstream of the junctions of the vena cava with the subject's renalveins. Typically, the occlusion element is configured to partiallyocclude the subject's vena cava upstream of the junctions of the venacava with the subject's renal veins. The occlusion element is configuredto partially occlude the subject's vena cava such that, in response tothe pumping of the downstream blood pump, there is not a substantialincrease of blood flow from the subject's lower body toward the subjectheart, but such that a region of low pressure within the vena cava isgenerated, between the occlusion element and the downstream blood pump,within which the blood pressure is lower than the subject's centralvenous pressure. Typically, by generating a region of low pressure,blood flow from the renal veins into the vena cava increases, therebylowering renal blood pressure and enhancing renal perfusion. It is notedthat the occlusion element is configured to partially occlude, but notto totally occlude, the vena cava, in such a manner as to generate aregion of low pressure within the vena cava, but to allow a substantialflow of blood through the vena cava

When blood-pump catheter 20 is used to enhance blood flow from the renalveins into the subject's vena cava, as described herein, a longitudinaldistance D2 between the longitudinal center of the impeller of thedownstream pump and the longitudinal center of the occlusion element,measured along the longitudinal axis of the catheter, is typically morethan 3 cm (e.g., more than 6 cm), and/or less than 18 cm (e.g., lessthan 14 cm), e.g., 3-18 cm, or 6-14 cm.

As used in the present application, including in the claims, a“longitudinal axis” of a structure is the set of all centroids ofcross-sectional sections of the structure along the structure. Thus thecross-sectional sections are locally perpendicular to the longitudinalaxis, which runs along the structure. (If the structure is circular incross-section, the centroids correspond with the centers of the circularcross-sectional sections.) As used in the present application, includingin the claims, the term “longitudinal center” denotes the center of astructure along the direction of the structure's longitudinal axis.

For some applications, the occlusion element is balloon 80, as shown inFIG. 5A. Alternatively or additionally, the occlusion element is coveredframe 82, as shown in FIG. 5B. For example, the frame may be a rigidframe made of a shape-memory element (such as nitinol) that is coveredwith a blood-impermeable material 83 (e.g., polyester, polyurethane,and/or a different polymer).

As described hereinabove, typically, the occlusion element is configuredto partially occlude the vena cava upstream of the junctions of the venacava with the subject's renal veins. For some applications, the diameterto which the occlusion element is expanded is controllable. For example,inflation of the balloon may be controllable, or the stent may beexpandable (e.g., by heating the stent, or by applying an electricalcurrent to the stent). For some applications, the extent to which theocclusion element occludes the vena cava is controlled by a control unit(e.g., control unit 52) responsively to the blood pressure detected byblood pressure sensor 56, 58, and/or 60, in response to an input from adifferent sensor (such as a flow sensor and/or an oxygen-saturationsensor, and/or a thermal flow sensor, e.g., as described with referenceto FIGS. 22Ai-Cii of WO 14/141284 to Schwammenthal, which isincorporated herein by reference), and/or in response to an input from auser. For some applications, the rate at which pump 24D pumps blood awayfrom the renal veins (e.g., the rate at which impeller 28 of the pump isrotated), as well as the extent to which the occlusion element occludesthe vena cava is controlled by a control unit responsively to the bloodpressure detected by blood pressure sensor 56, 58, and/or 60, inresponse to an input from a different sensor (such as a flow sensorand/or an oxygen-saturation sensor, and/or a thermal flow sensor, e.g.,as described with reference to FIGS. 22Ai-Cii of WO 14/141284 toSchwammenthal, which is incorporated herein by reference), and/or inresponse to an input from a user.

Although FIGS. 5A and 5B show the downstream blood pump and theocclusion element disposed on a catheter that is inserted into the venacava from above the junctions of the vena cava with the subject's renalveins (e.g., via the subject's subclavian vein or jugular vein), forsome applications, the downstream blood pump and the occlusion elementare disposed on a catheter that is inserted into the vena cava frombelow the junctions of the vena cava with the subject's renal veins(e.g., via the subject's femoral vein), mutatis mutandis. Alternativelyor additionally, the occlusion element is disposed on a first catheterwhich is inserted into the vena cava from below the junctions of thevena cava with the subject's renal veins (e.g., via the subject'sfemoral vein), and the downstream blood pump is disposed on a secondcatheter, which inserted into the vena cava from above the junctions ofthe vena cava with the subject's renal veins (e.g., via the subject'ssubclavian vein, or jugular vein).

Reference is now made to FIG. 6, which is a schematic illustration of ablood-impermeable sleeve 84 configured to occlude blood flow from asubject's vena cava to the subject's renal veins, as described in WO14/141284, which is incorporated herein by reference. Typically, thesleeve is placed within the vena cava such that a downstream end 86 ofthe sleeve is coupled to the wall of the vena cava at a first location88 that is downstream of all renal veins 42 of the subject (e.g., leftand right renal vein in a typical subject that has two renal veins), andsuch that an upstream end 90 of the sleeve is coupled to a wall of thevena cava at a second location 92 that is upstream of all renal veins ofthe subject. Thus, the sleeve isolates the blood in the renal veins intoa compartment that is separated from blood flow through the center ofthe vena cava. Typically, a rigid structure, e.g., a stent 94 as shown,is configured to couple the upstream and downstream ends of the sleeveto the vena cava.

A pump 96 is configured to pump blood through inlet holes 97, from alocation that is exterior to sleeve 98 (i.e., from the isolatedcompartment) to a location that is in fluid communication with theinterior of the sleeve (e.g., a location within the vena cava upstreamor downstream of the sleeve). Thus, the pump pumps blood out of thesubject's renal veins and into the subject's vena cava. The sleeveprevents backflow of blood from the vena cava into the renal veins.

For some applications, sleeve 84 and stent 94 are inserted into thesubject's vena cava, while a guidewire 99 is disposed inside apump-accommodating sleeve 95. Subsequent to anchoring sleeve 84 andstent 94 to the vena cava, pump 96 is inserted through thepump-accommodating sleeve, by advancing the pump over the guidewire.

Sleeve 84 and pump 96 are generally as described with reference to FIGS.10A-D of WO 14/141284 to Schwammenthal, which is incorporated herein byreference.

It is noted that the effect of inserting sleeve 84 into the vena cavaand activating pump 96 in the described manner is that a low-pressureregion is generated within the subject's vena cava, adjacent tojunctions of the vena cava with the subject's renal veins, bloodpressure within the low-pressure region being lower than central venouspressure of the subject. Similarly, by using blood-pump catheter 20 asdescribed with reference to FIGS. 1A-5B, a low-pressure region isgenerated within the subject's vena cava, adjacent to junctions of thevena cava with the subject's renal veins, blood pressure within thelow-pressure region being lower than central venous pressure of thesubject. The effect of generating the low-pressure region within thevena cava is typically that blood flow from the renal veins to the venacava is increased, thereby reducing renal venous pressure, andincreasing renal perfusion.

In general, in the specification and in the claims of the presentapplication, the term “proximal” and related terms, when used withreference to a device or a portion thereof, should be interpreted tomean an end of the device or the portion thereof that, when insertedinto a subject's body, is typically closer to a location through whichthe device is inserted into the subject's body. The term “distal” andrelated terms, when used with reference to a device or a portionthereof, should be interpreted to mean an end of the device or theportion thereof that, when inserted into a subject's body, is typicallyfurther from the location through which the device is inserted into thesubject's body.

In general, in the specification and in the claims of the presentapplication, the term “downstream” and related terms, when used withreference to a blood vessel, or with reference to a portion of a devicethat is configured to be placed inside a blood vessel, should beinterpreted to mean a location within the blood vessel, or a portion ofthe device that is intended for placement at a location within the bloodvessel, that is downstream, with respect to the direction of antegradeblood flow through the blood vessel, relative to a different locationwithin the blood vessel. The term “upstream” and related terms, whenused with reference to a blood vessel, or with reference to a portion ofa device that is configured to be placed inside a blood vessel, shouldbe interpreted to mean a location within the blood vessel, or a portionof the device that is intended for placement at a location within theblood vessel, that is upstream with respect to the direction ofantegrade blood flow through the blood vessel, relative to a differentlocation within the blood vessel.

It is noted that blood pumps 24U and 24D, the catheters upon which theblood pumps are disposed (e.g., blood-pump catheter 20, catheter 66, andcatheter 68), and the occlusion elements described with reference toFIGS. 5A-B, and other devices described herein, are generally describedas being placed within the subject's vena cava, such that the upstreampump or the occlusion element is disposed upstream of junctions of thevena cava with the subject's renal veins, and the downstream pump isdisposed downstream of the junctions of the vena cava with the subject'srenal veins. However, it is noted that the scope of the presentinvention includes placing upstream pump 24U or the occlusion element inany main vein upstream of a tributary venous system, and placingdownstream pump 24D downstream of said tributary venous system, andconfiguring the pump(s) (e.g., via the direction of rotation ofimpellers of the pumps, or the orientation of the pumps) to generatepreferential flow from the tributaries into the main vein, mutatismutandis. For example, the pump(s) could be used to generate flow fromthe subject's hepatic veins into the subject's vena cava, in order toincrease perfusion of the subject's liver, mutatis mutandis. For someapplications, the upstream pump or the occlusion element is placedwithin a main vein upstream of two or more tributary venous systems intothe main vein (e.g., within the vena cava upstream of the renal venoussystem and the hepatic venous system). The downstream pump is placeddownstream of the two or more tributary venous systems. The pump(s) areconfigured to generate preferential flow from both of the tributaryvenous systems into the main vein by pumping blood through the mainvein, in the manner described herein.

For such applications, upstream pump 24U or the occlusion element isplaced in a main vein upstream of a tributary venous system, anddownstream pump 24D is placed downstream of said tributary venoussystem, and the pump(s) are configured (e.g., via the direction ofrotation of impellers of the pumps, or the orientation of the pumps) toreduce flow from the tributaries into the main vein. For some suchapplications, the blades of the downstream impeller are oriented suchthat, as the downstream impeller is rotated, the downstream impellerpumps in the upstream direction (toward the junction between thetributary system and the main vein). The blades of the upstream impellerare oriented such that, as the upstream impeller rotates is rotated, theupstream impeller pumps in the downstream direction (toward the junctionbetween the tributary system and the main vein).

For some applications, the upstream and downstream pumps 24U and 24D,the catheter(s) upon which the blood pumps are disposed (e.g.,blood-pump catheter 20, catheter 66, and catheter 68), and/or theocclusion elements described with reference to FIGS. 5A-B, and otherdevices described herein, are placed within a main artery upstream anddownstream of bifurcations of the artery with one or more branchingarterial systems that branch from the main artery and supply a givenorgan, mutatis mutandis. For such applications, the upstream pump istypically configured to pump in the downstream direction (toward thebifurcations) and the downstream pump is configured to pump in theupstream direction (toward the bifurcations), such that blood flow intothe branching arterial system is increased, thereby increasing perfusionof the organ. Alternatively or additionally, the occlusion element isplaced downstream of the bifurcations of the artery with the one or morearterial systems and is configured to partially occlude the arterydownstream of the bifurcations. For example, the upstream pump may beplaced in the subject's aorta upstream of the subject's renal arteriesand the downstream pump may be placed in the subject's aorta downstreamof the subject's renal arteries, the pumps acting to pump blood into therenal arteries and toward the subject's kidneys. For some applications,upstream and downstream pumps, and/or occlusion elements are placed onboth the arterial and venous sides of the subject's body in order toincrease perfusion of a given organ or set of organs, in the mannerdescribed herein.

Although some applications of the present invention are described withreference to blood pumps 24D and 24U, according to which the blood pumpsinclude impellers, the scope of the present invention includes using anyother type of pump for pumping blood in the manner described herein,mutatis mutandis. For example, a roller pump, an Archimedes screw pump,a centrifugal pump, a pneumatic pump, and/or a compression pump may beused.

The scope of the present invention includes combining any of theapparatus and methods described herein with any of the apparatus andmethods described in one or more of the following applications, all ofwhich are incorporated herein by reference:

International Patent Application PCT/IL2014/050289 to Schwammenthal(published as WO 14/141284), filed Mar. 13, 2014, entitled “Renal pump,”which claims priority from (a) U.S. Provisional Patent Application61/779,803 to Schwammenthal, filed Mar. 13, 2013, entitled “Renal pump,”and (b) U.S. Provisional Patent Application 61/914,475 to Schwammenthal,filed Dec. 11, 2013, entitled “Renal pump;” and

International Patent Application PCT/IL2013/050495 to Tuval (publishedas WO 13/183060), filed Jun. 6, 2013, entitled “Prosthetic renal valve,”which claims priority from U.S. Provisional Patent Application61/656,244 to Tuval, filed Jun. 6, 2012, entitled “Prosthetic renalvalve.”

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. Apparatus comprising: a catheter configuredto be placed inside a blood vessel of a subject; a blood pump disposedon the catheter; and an occlusion element disposed on the catheter, andconfigured to partially occlude the subject's blood vessel, the bloodpump and the occlusion element being separated from one another along alongitudinal axis of the catheter, and the blood pump and the occlusionelement being configured to generate a region within the blood vesselthat is of lower blood pressure than elsewhere within the blood vesselby the blood pump pumping away from a region of the blood vessel betweenthe blood pump and the occlusion element.
 2. The apparatus according toclaim 1, wherein the blood pump comprises an impeller configured to pumpblood through the subject's blood vessel by rotating.
 3. The apparatusaccording to claim 2, further comprising a cage, the impeller beingdisposed inside the cage, and the cage being configured to maintain aseparation between the impeller and an inner wall of the blood vessel.4. The apparatus according to claim 1, wherein the catheter isconfigured to be placed within a vena cava of a subject such that theblood pump is disposed downstream of junctions of the vena cava with allrenal veins of the subject, and such that the occlusion element isdisposed upstream of junctions of the vena cava with all renal veins ofthe subject.
 5. The apparatus according to claim 4, wherein the bloodpump is configured to lower pressure within the subject's renal veins bypumping blood through the vena cava in a downstream direction.
 6. Theapparatus according to claim 4, wherein the catheter is configured to beplaced within the subject's vena cava by being inserted via a vein ofthe subject selected from the group consisting of: a subclavian vein, ajugular vein, and a femoral vein.
 7. The apparatus according to claim 1,wherein the catheter is configured to be placed within a vein of asubject into which a tributary vessel flows such that: the blood pump isplaced in the vein, downstream of the tributary vessel; and theocclusion element is placed in the vein, upstream of the tributaryvessel.
 8. The apparatus according to claim 1, wherein the occlusionelement comprises a balloon.
 9. The apparatus according to claim 1,wherein the occlusion element comprises a frame at least partiallycovered with a blood impermeable material.
 10. Apparatus comprising: acatheter configured to be placed inside a vena cava of a subject; ablood pump disposed on the catheter; and an occlusion element disposedon the catheter, and configured to partially occlude the subject's bloodvessel, the blood pump and the occlusion element being separated fromone another along a longitudinal axis of the catheter, and the catheterbeing configured to be placed within the subject's vena cava, such thatthe blood pump is disposed downstream of junctions of the vena cava withrenal veins of the subject, and such that the occlusion element isdisposed upstream of junctions of the vena cava with the subject's renalveins.
 11. The apparatus according to claim 10, wherein the blood pumpcomprises an impeller configured to pump blood through the subject'sblood vessel by rotating.
 12. The apparatus according to claim 10,wherein the occlusion element comprises a balloon.
 13. The apparatusaccording to claim 10, wherein the occlusion element comprises a frameat least partially covered with a blood impermeable material.